DESCRIPTION: PRELIMINARY STUDY: Noncompliance is the leading cause of nonresponse to drug. This 1-year preliminary study randomly assigns 80 outpatients with alcohol dependence to 2 strategies for monitoring compliance (Medication Event Monitoring System [MEMS] vs. blister pack) in relation to plasma levels of naltrexone and 6-beta-naltrexol, and to 2 strategies for enhancing compliance (compliance counseling vs. usual care) in a 2X2 design. All subjects receive 8 weeks of Medication Management Therapy (MMT) and naltrexone to assess acceptability and rate of compliance with the dosing regimen and minimally intensive therapy condition proposed for the main study. MAIN STUDY: New advances in outpatient pharmacologic and behavioral treatments of alcohol dependence have generally occurred independently of each other. The objective of the main study is to evaluate the relative efficacy of combined treatments in a 2X4 multicenter, double-blind, randomized, placebo-controlled comparison of 4 pharmacotherapy conditions (acamprosate, naltrexone, placebo, and acamprosate/naltrexone in combination) administered in conjunction with either the cognitive behavioral therapy typically administered by an alcoholism treatment specialist, or a manualized MMT that may be suitable for managed care settings. Primary outcome measures are time to first drink, time to first heavy drinking day, and cumulative abstinence duration. Treatment duration is 6 months with 1 year of posttreatment follow-up. Subjects for the multicenter study are 1200 outpatients meeting DSM IV criteria for alcohol dependence, recruited across 6-8 centers. NONRESPONDER STUDY: A response evaluation will be made at 3 months post-randomization in the main study. Approximately 400 nonresponders to active medication will be available for a 12-week comparison of alternative pharmacotherapy strategies commonly used in general clinical practice. All other subjects will remain in the originally assigned treatment condition in the main study. Nonresponders to monotherapy will be randomized to the alternative monotherapy or combination treatment, nonresponders to combination treatment will be randomized to increased doses of acamprosate or naltrexone.